Comparing Pulmonary Vein Isolation to Pulmonary Vein Isolation + OPTIMA Ablation in Patients Undergoing Ablation for Atrial Fibrillation (OPTIMA)
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|ClinicalTrials.gov Identifier: NCT04101539|
Recruitment Status : Active, not recruiting
First Posted : September 24, 2019
Last Update Posted : September 25, 2020
Catheter ablation is an established cornerstone of therapy for patients with symptomatic atrial fibrillation (AF) who wish to avoid anti-arrhythmic drug therapy or for whom anti-arrhythmics have proven ineffective. Pulmonary vein isolation (PVI), in which circumferential ablation is performed around the ostia of the pulmonary vein - left atrial junctions, is the standard ablation approach internationally. Single-procedure success rates (1y, freedom from AF, off anti-arrhythmics) for patients with paroxysmal AF is roughly 70%, and even worse (roughly 50%) for patients with persistent AF.
A number of strategies have been developed to improve outcomes in patients undergoing AF ablation, particularly in patients with persistent AF. Unfortunately, large prospective randomized trials (including STAR-AF II, published in NEJM in 2015) have demonstrated a failure of ancillary ablation techniques to improve AF ablation outcomes relative to PVI alone.
In a collaborative effort between the Cardiology electrophysiology group and the Trayanova laboratory (Biomechanical Engineering), investigators have developed a strategy of patient-specific modeling to identify pro-arrhythmic sites in AF patients that may be amenable to ablation. In this approach, patients undergo a pre-ablation cardiac MRI with late gadolinium enhancement, to delineate regions of healthy atrial tissue and regions of scar (this scan is clinically indicated, and performed currently in patients undergoing PVI for AF). A novel in silico modeling to determine regions supporting electrical reentry in the atrium, driving ongoing AF, has been developed by the Trayanova lab. In preliminary studies, investigators have demonstrated the ability to identify and target these regions with catheter ablation in patients undergoing PVI.
Investigators would like to conduct a prospective, randomized clinical trial in patients undergoing ablation for symptomatic persistent AF. All patients enrolled would undergo standard pre-procedure imaging (LGE-MRI) prior to the day of procedure. Investigators have developed methodology termed OPTIMA (OPtimal Target Identification via Modeling of Arrhythmogenesis) to determine, based on non-invasive patient-specific anatomic and tissue data from late gadolinium enhancement cardiac MRI (LGE-CMR) and simulation of cardiac electrical function, personalized ablation targets for persistent AF in patients with fibrotic remodeling.. Patients would be randomized to receiving PVI only versus PVI + OPTIMA ablation at the time of ablation. Patients would then be followed in standard clinical fashion at 3m, 6m, and 12m to assess for ablation efficacy and for procedural complications.
Investigators postulate a 20% improvement in freedom from AF with PVI + OPTIMA ablation form 50% to 70% (compared to PVI alone), investigators anticipate that in 1:1 randomization, a sample size of 80 patients in each arm will yield a power calculation of 80% with an alpha of 0.05. Investigators anticipate that enrollment and 1y clinical follow-up for 160 patients (total) undergoing AF ablation will require a 4y timeline.
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation Chronic||Device: OPTIMA-guided catheter ablation Device: Standard PVI||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Prospective, randomized, controlled|
|Masking:||Double (Participant, Outcomes Assessor)|
|Masking Description:||Blinding of patient and outcomes assessor to ablation protocol.|
|Official Title:||A Randomized Trial Comparing Pulmonary Vein Isolation to Pulmonary Vein Isolation + OPTIMA Ablation in Patients Undergoing Ablation for Atrial Fibrillation|
|Actual Study Start Date :||September 1, 2019|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2022|
Active Comparator: Standard Ablation (PVI)
Patients in this arm will receive standard ablation for atrial fibrillation (wide-area circumferential ablation to achieve pulmonary vein isolation [PVI]).
Device: Standard PVI
Standard PVI for AF.
Experimental: OPTIMA Ablation
Patients in this arm will receive standard PVI ablation and supplemental ablation of reentrant driver sites identified by OPTIMA analysis as sites likely supportive of persistent atrial fibrillation.
Device: OPTIMA-guided catheter ablation
Patients in the experimental arm will undergo supplemental ablation of OPTIMA-identified sites hypothesized to support/perpetuate chronic atrial fibrillation.
- Freedom from atrial arrhythmias (>30s) [ Time Frame: 1 year ]Freedom from recurrent Atrial fibrillation (AF)/Atrial Tachycardia (AT)/Atrial Flutter (> 30s) after 90 day blanking period. This will be measured as the percentage of the study population that is free from atrial arrhythmias during the 1y follow-up period.
- Change in AF burden [ Time Frame: 1 year ]This will measure the change in percentage time spent in AF for each study patient after ablation (baseline is the pre-ablation percentage time in AF). The change in AF burden for the overall study population will be calculated and expressed.
- Percent participants with 70% or more reduction in AF burden [ Time Frame: 1 year ]This will be a measure of the number of patients in each study group that achieve at least a 70% reduction in their baseline AF burden. This outcome will be expressed as a percentage of the number of patients in each study group meeting this outcome.
- Freedom from major complications [ Time Frame: 1 year ]This is a comparison of the percentage of patients in each study arm suffering a major complication. Complications including the following: death, stroke, cardiac tamponade, atrial-esophageal fistula, vascular injury, hemorrhage, cardiac injury, myocardial infarction, or other major complications resulting in either reparative procedure or prolonged hospitalization. Outcome will be expressed as a ratio.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04101539
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||David Spragg, MD||Johns Hopkins University|